6byl

Publication Abstract from PubMed

O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins. We identified several human proteins, including 14-3-3 isoforms, that bind O-GlcNAc directly and selectively. We demonstrate that 14-3-3 proteins bind O-GlcNAc moieties in human cells, and we present the structures of 14-3-3beta/alpha and gamma bound to glycopeptides, providing biophysical insights into O-GlcNAc-mediated protein-protein interactions. Because 14-3-3 proteins also bind to phospho-serine and phospho-threonine, they may integrate information from O-GlcNAc and O-phosphate signaling pathways to regulate numerous physiological functions.

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.,Toleman CA, Schumacher MA, Yu SH, Zeng W, Cox NJ, Smith TJ, Soderblom EJ, Wands AM, Kohler JJ, Boyce M Proc Natl Acad Sci U S A. 2018 May 21. pii: 1722437115. doi:, 10.1073/pnas.1722437115. PMID:29784830^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.